Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of urapidil and aripiprazole in human plasma and its application to human pharmacokinetic study.

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of urapidil and aripiprazole in human plasma. A simple liquid-liquid extraction with ethyl acetate was used for the sample preparation. Chromatographic separation was achieved on a Phenomenex C18 (4.6 × 50 mm, 5 µm) column with 0.1% formic acid-acetonitrile (10:90, v/v) as the mobile phase with flow rate of 0.6 mL/min. The quantitation of the target compounds was determined in a positive ion multiple reaction monitoring mode. Calibration plots were linear over the range of 2.0-2503.95 ng/mL for urapidil and 1.0-500.19 ng/mL for aripiprazole. The lower limit of quantitation for urapidil and aripiprazole was 2.0 and 1.0 ng/mL, respectively. Mean recovery was in the range of 69.94-75.62% for both analytes and internal standards. Intra-day and inter-day precisions of the assay at three concentrations were 2.56-5.89% with accuracy of 92.31-97.83% for urapidil, and 3.14-6.84% with accuracy of 91.38-94.42% for aripiprazole. The method was successfully applied to human pharmacokinetic study of urapidil and aripiprazole in healthy human male volunteers.